Human fertility is a complex trait with multiple genetic and environmental determinants. However, the genes involved in human female fertility, in particular the formation and maintenance of oocytes (eggs), have yet to be discovered. Over the course of a woman's lifetime her oocytes/follicles are continually lost through the process of atresia (cell death) and ovulation. There is great variability in the quality and quantity of the oocyte pool, or ovarian reserve, among women. We hypothesize that the ovarian reserve is largely determined by genetic factors that impact early germ cell and oocyte formation. By combining classical human genetics, a cutting edge genome-wide microarray approach, and novel stem cell biology approaches my research plan aims to identify the genetic factors that are associated with oocyte/follicle number and quality at both the population and cellular level in women. Specifically, we aim to determine the associations between common genetic variants and a woman's antral follicle count, and how various environmental/anthropometric factors and ethnicity affect follicle numbers. This study will include a large recruited sample of ethnically-diverse women, ages 25-45. Using ultrasound imaging of the ovaries we will assess each woman's antral follicle count (AFC), which is an indicator of the number of remaining eggs she has. Detailed lifestyle and health questionnaires, body measurements, and blood samples for hormonal and genetic analyses, will be collected. A genome-wide microarray approach that includes over 1.8 million markers for single nucleotide polymorphisms and copy number variants will be used to identify genes and chromosomal regions likely to be linked with the oocyte reserve. The functional roles of particularly strong genetic links will be explored using our novel in vitro embryonic stem cell-germ cell system. Ultimately, the goals are to translate our findings into clinical applications;to use AFC and genetic markers to prospectively identify women at risk for premature decline in the ovarian reserve and infertility.